Bilateral chylothorax following left neck dissection and literature review.

Chylothorax without chyle cervical leakage after neck dissection it is extremely rare. We report a case of bilateral chylothorax without chyle cervical leakage after left neck dissection, wherein partial left upper jaw resection and left radical neck dissection were performed in a 46-year-old woman who was diagnosed with left upper gingival cancer. The thoracic duct was ligated and cut during surgery and, although no obvious leakage of lymph was observed, dyspnea and cough reflex during deep inhalation were observed from the third postoperative day. Approximately 600 mL of yellowish-white pleural effusion was aspirated during bilateral thoracentesis, and chylothorax was diagnosed based on clinical findings and biochemical analysis results. The patient was put on a low-fat diet on the fourth postoperative day. Pleural effusion disappeared on imaging examination 16 days after thoracentesis.

Improving the Detection Sensitivity of a New Rapid Diagnostic Technology for Severe Acute Respiratory Syndrome Coronavirus 2 Using a Trace Amount of Saliva.

The early diagnosis and isolation of infected individuals with coronavirus disease 2019 (COVID-19) remain important. Although quantitative polymerase chain reaction (qPCR) testing is considered the most accurate test available for COVID-19 diagnosis, it has some limitations, such as the need for specialized laboratory technicians and a long turnaround time. Therefore, we have established and reported a rapid diagnostic method using a small amount of saliva as a sample using a lightweight mobile qPCR device. This study aimed to improve the existing method and increase the detection sensitivity and specificity. The detection specificity of CDC N1 and N2 was examined by improving qPCR reagents and polymerase chain reaction conditions for the previously reported method. Furthermore, the feasibility of detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA was examined using both the previous method and the improved method in patients with COVID-19. The results showed that the improved method increased the specificity and sensitivity. This improved method is useful for the rapid diagnosis of SARS-CoV-2.

[Successful treatment of secondary graft failure after allogeneic stem cell transplantation for aplastic anemia with eltrombopag].

Herein we report a case of successful treatment of secondary graft failure due to poor graft function (PGF) using eltrombopag. A 25-year-old woman with aplastic anemia (stage 3) underwent allogeneic bone marrow transplantation (BMT) from her HLA-matched brother. Neutrophil engraftment was achieved on day 17, but she remained dependent on platelet transfusion. Chimerism analysis showed complete donor type, but she also became dependent on red blood cell transfusion later. Eltrombopag was administered on day 253 after BMT, after which she exhibited hematopoietic recovery, resulting in the withdrawal of transfusion dependency. Blood counts continued to be stable after eltrombopag was discontinued. The use of eltrombopag enabled outpatient treatment and induced hematopoietic recovery without significant side effects. Eltrombopag may be an effective and safe option for PGF after BMT.

The Prognostic Impact of MYC Gene-Related Abnormalities on Multiple Myeloma Outcome through Fluorescence in situ Hybridization Analysis.

INTRODUCTION: Chromosomal abnormalities (CAs) have been identified as important factors in determining the biological features and prognostic value of multiple myeloma (MM). MYC gene-related abnormalities (MYC GAs) are one of the CAs, but their unfavorable impact has not been fully investigated in daily clinical practice. METHODS: This study retrospectively analyzed the prognostic impact of MYC GAs on 81 patients through fluorescence in situ hybridization analysis in our institute. RESULTS: MYC GAs were associated with poor overall survival (hazard ratio [HR], 3.08; 95% confidence interval [CI]: 1.23-7.73; p = 0.017), progression-free survival (PFS) (HR, 2.96; 95% CI: 1.58-5.53; p < 0.001), and time to next treatment (TNT) (HR, 2.11; 95% CI: 1.13-3.93; p = 0.018) in the median follow-up of 34.7 months. Furthermore, MYC GAs with an additional chromosome 8 (MYC-Ch8(+)) were associated with shorter PFS (HR, 3.15; 95% CI: 1.38-7.2; p = 0.0064), whereas MYC GAs without an additional chromosome 8 (MYC-Ch8(-)) were associated with shorter PFS (HR, 3.62; 95% CI: 1.51-8.68; p = 0.004) and shorter TNT (HR, 3.72; 95% CI: 1.41-9.81; p = 0.0078). CONCLUSION: These findings could help identify high-risk patients with MM. Further prospective studies are needed to confirm the significance of MYC GAs for the MM prognostic effect.

Feasibility of Rapid Diagnostic Technology for SARS-CoV-2 Virus Using a Trace Amount of Saliva.

Containment of SARS-CoV-2 has become an urgent global issue. To overcome the problems of conventional quantitative polymerase chain reaction (qPCR) tests, we verified the usefulness of a mobile qPCR device that utilizes mouthwash to obtain a saliva sample with the aim of developing a rapid diagnostic method for SARS-CoV-2. First, we examined whether anyone could easily operate this device. Then, we examined whether RNA in the mouthwash could be detected in a short time. In addition, we investigated whether it was possible to diagnose SARS-CoV-2 infection using mouthwash obtained from COVID-19 patients undergoing hospitalization. The results revealed that all subjects were able to complete the operation properly without error. In addition, RNase P was detected in the mouthwash without pretreatment. The average detection time was 18 min, which is significantly shorter than conventional qPCR devices. Furthermore, this device detected SARS-CoV-2 in the mouthwash of a COVID-19 patient undergoing hospitalization. The above findings verified the efficacy of this diagnostic method, which had a low risk of infection, was technically simple, and provided stable results. Therefore, this method is useful for the rapid detection of SARS-CoV-2.

Increased SLAMF7high monocytes in myelofibrosis patients harboring JAK2V617F provide a therapeutic target of elotuzumab.

Monocyte-derived fibrocytes recently garnered attention because the novel pathogenesis of myelofibrosis (MF), and suppression of fibrocyte differentiation by serum amyloid P remarkably improved MF. We previously revealed that human fibrocytes highly expressed signaling lymphocytic activation molecule F7 (SLAMF7) compared with macrophages and that SLAMF7high monocytes in the peripheral blood (PB) of MF patients were significantly elevated relative to those in healthy controls (HCs). In this study, we evaluated SLAMF7high monocyte percentage in the PB of HCs, myeloproliferative neoplasm (MPN) patients with MF, and MPN patients without MF by using a cross-sectional approach. We found that MPN patients with MF who harbored JAK2V617F had a significantly elevated SLAMF7high monocyte percentage, which correlated positively with the JAK2V617F allele burden. In addition, the serum concentration of interleukin-1ra (IL-1ra) was significantly correlated with the SLAMF7high monocyte percentage and JAK2V617F allele burden. These findings suggest that both SLAMF7high monocytes and IL-1ra could be useful noninvasive markers of MF onset. Furthermore, the JAK2V617F allele burden of SLAMF7high monocytes was significantly higher than that of SLAMF7low monocytes and could be a potential target of elotuzumab (Elo), an anti-SLAMF7 antibody used for treating multiple myeloma. Elo independently inhibited differentiation of fibrocytes derived not only from HCs but also from MF patients in vitro. Elo also ameliorated MF and splenomegaly induced by romiplostim administration in humanized NOG mice. In conclusion, an increase of SLAMF7high monocytes with higher JAK2V617F allele burden was associated with the onset of MF in MPN patients harboring JAK2V617F, and Elo could be a therapeutic agent for MPN patients with MF who harbor JAK2V617F.

Low mucosal-associated invariant T-cell number in peripheral blood of patients with immune thrombocytopenia and their response to prednisolone.

Mucosal-associated invariant T (MAIT) cells help protect against certain infections and are related to some autoimmune diseases. Immune thrombocytopenia (ITP) is a relatively rare hematological autoimmune disease associated with low platelet count. We designed a cross-sectional study wherein we examined peripheral blood samples of patients with ITP for the number of MAIT cells (CD3+TCR-Vα7.2+CD161+IL-18Rα+ lymphocytes) and their CD4/8 subsets (by flow cytometry) and levels of cytokines (by multiplex assays). The study cohort included 18 patients with ITP and 20 healthy controls (HCs). We first compared the number of MAIT cells between HCs and patients with ITP and then performed subgroup analysis in patients with ITP. The number of total MAIT cells in patients with ITP was significantly lower than that in HCs (p < 0.0001), and the CD4-CD8+ subset of MAIT cells showed the same trend. Moreover, patients with ITP refractory to prednisolone exhibited a significantly lower number of total MAIT and CD4-CD8+ MAIT cells than patients sensitive to prednisolone. The number of total MAIT and CD4-CD8+ MAIT cells was not correlated with the response to thrombopoietin receptor agonist treatment or with Helicobacter pylori infection. We found no relation between cytokine levels and response to prednisolone treatment, although the levels of IP-10 and RANTES showed a correlation with the number of total MAIT and CD4-CD8+ MAIT cells. In conclusion, total MAIT and CD4-CD8+ MAIT cells in peripheral blood were decreased in patients with ITP, correlating with their response to prednisolone.

Primary Nonsecretory Plasma Cell Leukemia With Multiple Chromosomal Abnormalities: A Case Report.

Primary nonsecretory plasma cell leukemia (PCL) is an extremely rare type of multiple myeloma. Here, we report a case of nonsecretory PCL with no previous history of multiple myeloma. The case exhibited extremely low levels of serum immunoglobulin and light chain, no detectable serum M-protein or free light chain restriction, no urine BJP, and no cytoplasmic light chain expression in flow cytometry. In fluorescence in situ hybridization, tumor cells exhibited fusion genes for IgH/BCL1 and IgH/cMyc, disappearance of the p53 signal, and a split signal for IgK(2p11), but no split signal for IgL (22q11). Therefore, we diagnosed primary nonsecretory PCL with multiple chromosomal abnormalities.

CBL mutation and MEFV single-nucleotide variant are important genetic predictors of tumor reduction in glucocorticoid-treated patients with chronic myelomonocytic leukemia.

Glucocorticoid (GC) therapy occasionally relieves tumor-related fever and promotes tumor reduction in patients with chronic myelomonocytic leukemia (CMML). A mutation analysis of 24 patients with CMML revealed the relationship of GC effectiveness, defined as a monocyte reduction of > 50% within 3 days of methylprednisolone administration, with the MEFV single-nucleotide variant (SNV) and CBL mutation. Lipopolysaccharide-stimulated monocytes harboring MEFV E148Q produced greater amounts of IL-1ß and TNF-α than did wild-type monocytes; this was effectively suppressed by GC. Primary CMML cells harboring the MEFV SNV and CBL mutation, and the myelomonocytic leukemia cell line GDM-1, harboring the CBL mutation, were both more significantly suppressed than non-mutated cells following GC treatment in the presence of GM-CSF. A loss-of-function CBL mutation prolonged STAT5 phosphorylation after GM-CSF stimulation, which was rapidly terminated in both patient samples and GDM-1 cells. In conclusion, GC therapy effectively treats CMML cells harboring the MEFV SNV and CBL mutation by reducing inflammatory cytokine production and terminating prolonged STAT5 phosphorylation in the GM-CSF signaling pathway.

Sudden blast phase in chronic myeloid leukemia developed during nilotinib therapy after major molecular response was achieved.

Sudden blast phase (SBP) is a rare event in which patients with chronic myeloid leukemia (CML) in complete cytogenetic response (CCyR) rapidly progress to the blast phase. Few patients on second-generation tyrosine kinase inhibitors (2nd TKIs) have been reported to develop SBP. Here, we report a 45-year-old man diagnosed with CML in the chronic phase in April 2008 and immediately started on imatinib therapy. He achieved CCyR 12 months after starting imatinib therapy. Imatinib was followed by treatment with the 2nd TKIs nilotinib and dasatinib from January 2011 to yield a better response. He achieved major molecular response (MMR) during dasatinib therapy in February 2012, but did not tolerate dasatinib well; hence, he was switched to nilotinib in July 2012. In December 2015, he presented at our hospital with fever and lumbago. A complete blood count revealed a white blood cell count of 30,500/µL with 60% blasts, leading to diagnosis of SBP. After dasatinib therapy and conventional chemotherapy, he again achieved MMR. This case demonstrates that SBP may occur after achieving MMR on treatment with 2nd TKIs. Continuous careful monitoring is required for the early detection of SBP, even in patients who have achieved MMR.

TAK1 inhibition ameliorates survival from graft-versus-host disease in an allogeneic murine marrow transplantation model.

Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in allogeneic hematopoietic cell transplantation (allo-HCT). Majority of the current immunosuppressive strategies targeting donor T cells to prevent or treat acute GVHD are only partially effective, and often require escalated immunosuppressive therapy. Recent studies have revealed that activation of antigen-presenting cells in the proinflammatory milieu is important for the priming and promotion of GVHD. This activation is mediated by innate immune signaling pathways, which therefore potentially represent new targets in addressing GVHD. Using gene expression analysis of peripheral monocytes from patients' post-allo-HCT, we detected an upregulation of TGF-ß-activated kinase 1 (TAK1), a key regulator of the toll-like receptor signaling pathway. 5Z-7-oxozeaenol, a selective inhibitor of TAK1, reduced proinflammatory cytokine production by activated monocytes under lipopolysaccharide stimulation and T cell proliferation in allogeneic-mixed leukocyte reactions with monocyte-derived dendritic cells. In an experimental mouse model of GVHD, 5Z-7-oxozeaenol administration after allo-HCT ameliorated GVHD severity and mortality, with significant reduction in serum TNFα, IL-1ß, and IL-12 levels. Our findings suggest that altering the activation status of innate immune cells by TAK1 inhibition may be a novel therapeutic approach for acute GVHD.

Fluorescence multispectral imaging-based diagnostic system for atherosclerosis.

BACKGROUND: Composition of atherosclerotic arterial walls is rich in lipids such as cholesterol, unlike normal arterial walls. In this study, we aimed to utilize this difference to diagnose atherosclerosis via multispectral fluorescence imaging, which allows for identification of fluorescence originating from the substance in the arterial wall. METHODS: The inner surface of extracted arteries (rabbit abdominal aorta, human coronary artery) was illuminated by 405 nm excitation light and multispectral fluorescence images were obtained. Pathological examination of human coronary artery samples were carried out and thickness of arteries were calculated by measuring combined media and intima thickness. RESULTS: The fluorescence spectra in atherosclerotic sites were different from those in normal sites. Multiple regions of interest (ROI) were selected within each sample and a ratio between two fluorescence intensity differences (where each intensity difference is calculated between an identifier wavelength and a base wavelength) from each ROI was determined, allowing for discrimination of atherosclerotic sites. Fluorescence intensity and thickness of artery were found to be significantly correlated. CONCLUSIONS: These results indicate that multispectral fluorescence imaging provides qualitative and quantitative evaluations of atherosclerosis and is therefore a viable method of diagnosing the disease.

Elevated total iron-binding capacity as a predictor of response to deferasirox therapy in the setting of chronic iron overload.

It is difficult to predict the efficacy of deferasirox (DFX) as its pharmacokinetics varies among patients. The area under the curve (AUC) is reportedly useful for determining adequate DFX dosage; however, serum concentration measurements are often challenging. Effective DFX dosage is thus defined by assessing the efficacy of this agent in clinical practice. To analyze a predictive response marker to DFX therapy for use in adjusting the effective dosage during the early treatment phase, we retrospectively evaluated 39 DFX-treated patients. We defined response as a >40 % decrease in serum ferritin concentration from the pretreatment level. A maximum elevation of the total iron-binding capacity (TIBC) correlated with response in a multivariate analysis of iron metabolic markers (R (2) = 0.37, p < 0.001). A receiver operating characteristic curve analysis revealed that TIBC elevation had an AUC of 0.85 (p < 0.001) and the optimal cut-off value of TIBC elevation was 150 µg/dl. TIBC elevation of >150 µg/dl is a favorable predictor of effective ferritin reduction in DFX therapy (hazard ratio 29.6, 95 % confidence interval 4.8-183.6; p < 0.001). DFX therapy with TIBC monitoring may enable the determination of the minimum effective DFX dosage.

Mandibular reconstruction using custom-made titanium mesh tray and particulate cancellous bone and marrow harvested from bilateral posterior ilia.

The objective of this study is to evaluate usefulness of mandibular reconstructions using a custom-made titanium mesh (Ti-mesh) tray and particulate cancellous bone and marrow (PCBM). A consecutive nine patients who underwent mandibular reconstruction were enrolled in this study. They were five men and four women (mean age: 53.9 years). Virtual reality simulation was performed using computer software based on the pre-operative computed tomography data. A 3-dimensional (3-D) skull model was constructed using a 3-D printer. A tray was custom-made from a Ti-mesh sheet bent to adapt to the model. After PCBM harvesting from bilateral posterior ilia, the tray was fixed to the host bone. New bone formation and configuration of the reconstructed mandible were assessed radiologically. Complications were recorded in each patient during the follow-up period. Patients, satisfaction with post-operative facial contour was evaluated using a visual analogue scale (VAS score, range = 0-100). In six of nine patients, excellent new bone formation was recognised and expected results were radiologically achieved. Complications occurred in four patients. These complications included Ti-mesh fracture, Ti-mesh exposure in the oral cavity, and delayed infection. Mean VAS score on patient satisfaction was 77.6. Although the data are preliminary, the results suggest that this method is clinically useful.

Immunohistochemistry of cytokeratins 7, 8, 17, 18, and 19, and GLUT-1 aids differentiation of desmoplastic malignant mesothelioma from fibrous pleuritis.

It is difficult to distinguish desmoplastic malignant mesothelioma (DMM) from fibrous pleuritis (FP). We investigated the utility of immunohistochemistry as a way of differentiating between DMM and FP. We examined 11 DMMs and 46 FPs with the aid of antibodies against 18 cytokeratin (CK) subtypes, calponin, caldesmon, desmin, and GLUT-1. The best sensitivity and specificity cut-off values in the receiver operating characteristic curves (ROC) for CKs 7, 8, 17, 18, and 19, and GLUT-1 were each above 60%. When cases with either DMM or FP were partitioned by the staining score associated with the best sensitivity and specificity cut-off values in ROC, the incidence of a positive expression for CKs 7, 8, 17, 18, and 19, and GLUT-1 was significantly higher in DMM than in FP. In conclusion, immunohistochemistry for CKs 7, 8, 17, 18, and 19, and GLUT-1 may be useful, alongside histological characteristics, for separating DMM from FP.

The changes of joint effusion on MRI and arthroscopic findings after visually guided TMJ irrigation correlated to the clinical outcome.

OBJECTIVE: This study aimed to investigate the changes of joint effusion (JE) on the MRI and arthroscopically observed pathology after visually guided TMJ irrigation (VGIR) in patients with chronic closed lock. The correlation of these findings to the clinical outcome was also studied. STUDY DESIGN: Forty patients with unilateral chronic closed lock who underwent 2-time VGIR, were divided into either the good outcome (g-) group (n = 29) or poor outcome (p-) group (n = 11) after the first VGIR. Before each VGIR, the each severity of JE, osteoarthritis, synovitis, and fibrous adhesion were assessed. They were compared between the g- and p-groups, or between the first and second VGIR. RESULTS: The severity of JE at the first VGIR was significantly worse in the p-group. In both groups, JE significantly improved after the first VGIR. In the g-group, synovitis significantly improved after the first VGIR, but fibrous adhesion significantly became worse. CONCLUSIONS: JE may be predictive for the clinical outcome of TMJ irrigation in chronic closed lock patients. Moreover, the severity of JE and arthroscopically observed synovitis could reflect the clinical state to some degree.

Two-stage orthognathic treatment of severe class III malocclusion: report of a case.

We report a two-stage orthognathic operation for a 16-year-old boy with a repaired isolated cleft palate. He had a severe class III malocclusion with an overjet of 20.4 mm. In the first stage, we did an anterior subapical segmental osteotomy with symphyseal ostectomy to reposition the mandibular anterior segment posteriorly and to reduce the transverse width of the mandible. During the second stage, we did a maxillary advancement by Le Fort I osteotomy, mandibular set-back by sagittal split osteotomy, reduction genioplasty, and shortening of the tongue. This unique two-stage surgical and orthodontic treatment considerably improved his overall facial aesthetics and occlusion.